1. Field of the Invention
The present invention relates to the use of imidazo[1,2-b]pyridazine compounds to control parasites in animals and methods of treating parasite infestation in animals using the compounds.
2. Background
The control of animal parasites is important, especially in the areas of animal husbandry, as well as for companion animals. Existing methods of treatment are being compromised due to the growing resistance to current classes of parasiticides, such as the benzimidazoles and ivermectins. Therefore, there is a need to discover and/or identify new and more effective ways to control parasites of animals.
Derivatives of the imidazo[1,2-b]pyridazine ring system have been reported in the chemical literature and some general synthetic routes to compounds of this type have been reviewed [Hajos, G., Riedl, Z., Science of Synthesis, 2002, 12, 613-678; Barlin, G. B., Journal of Heterocyclic Chemistry, 1998, 35, 1205]. A range of pharmaceutically useful biological activities has also been reported for some imidazo[1,2-b]pyridazine derivatives [Barlin, G. B., Journal of Heterocyclic Chemistry, 1998, 35, 1205]. In the general area of parasite control, however, U.S. Pat. No. 3,905,974 discloses compounds of Formula A:
wherein
X is selected from hydroxy, mercapto, alkoxy (C1-C8), alkylthio (C1-C8), phthalimidoloweralkoxy, phenylloweralkoxy, lower alkoxyloweralkoxy, hydroxyloweralkoxy, loweralkenyloxy, halobenzoylloweralkoxy;
Z is nitro; and
Y is hydrogen or lower alkyl, where “lower” alkyls are those having 1 to 4 carbon atoms. The compounds are mentioned as having anti-protozoal, such as anti-amoebic and anti-trichomonal activity.
Fabio, Lanzilotti and Lang, Journal of Labelled Compounds and Radiopharmaceuticals, 1978, XV, 407-412, disclose another compound of Formula A in which X is propoxy, Y is hydrogen and Z is nitro. The compound is said to show amoebicidal and trichomonacidal activity.
Townsend, Mourad and Wise, in Journal of Heterocyclic Chemistry, 1992, 29, 1583-1592, describe a set of compounds corresponding to Formula A that were evaluated as potential antifilarial agents. In these compounds X is either CH3, CO2H, CO2Me, CO2CH2CH2CH3, CO2CH(CH3)2, CO2C(CH3)3, CONH2, 2-thienylcarbonyl, benzoyl or 4-fluorobenzoyl; Y is either tert-butyl or CONHMe; and Z is either hydrogen or bromine.
Townsend, Mourad and Wise, in Journal of Heterocyclic Chemistry, 1993, 30, 1365-1375, describe another set of compounds corresponding to Formula A which were evaluated as potential antifilarial agents. In these compounds, X is either phenylthio, phenylsufinyl, phenylsulfonyl, NHCO(2-fluorophenyl), NHCO (3-fluorophenyl), NHCO(4-fluorophenyl), NH2, NHNH2, NHC(═S)O (i-C3H7), NHC(═O)SCH3; Y is either methyl, tert-butyl, or NHCO2CH3; and Z is hydrogen.
Despite the forgoing, work has continued in this area in the attempt to find improved methods of treating diseases due to parasites, as well as to identify compounds that are useful in this treatment and for related purposes. The present invention addresses these needs.
The citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.